6SAK

Structure of the OTULINcat C129A - SNX27 PDZ domain complex.

6SAK の概要

• エントリーDOI: 10.2210/pdb6sak/pdb
• 分子名称: Ubiquitin thioesterase otulin, Sorting nexin-27, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: met1-specific deubiquitinase, hydrolase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 85643.68

構造登録者

Elliott, P.R.,Komander, D. (登録日: 2019-07-17, 公開日: 2019-10-02, 最終更新日: 2024-01-24)

主引用文献

Stangl, A.,Elliott, P.R.,Pinto-Fernandez, A.,Bonham, S.,Harrison, L.,Schaub, A.,Kutzner, K.,Keusekotten, K.,Pfluger, P.T.,El Oualid, F.,Kessler, B.M.,Komander, D.,Krappmann, D.
Regulation of the endosomal SNX27-retromer by OTULIN.
Nat Commun, 10:4320-4320, 2019

PubMed Abstract: OTULIN (OTU Deubiquitinase With Linear Linkage Specificity) specifically hydrolyzes methionine1 (Met1)-linked ubiquitin chains conjugated by LUBAC (linear ubiquitin chain assembly complex). Here we report on the mass spectrometric identification of the OTULIN interactor SNX27 (sorting nexin 27), an adaptor of the endosomal retromer complex responsible for protein recycling to the cell surface. The C-terminal PDZ-binding motif (PDZbm) in OTULIN associates with the cargo-binding site in the PDZ domain of SNX27. By solving the structure of the OTU domain in complex with the PDZ domain, we demonstrate that a second interface contributes to the selective, high affinity interaction of OTULIN and SNX27. SNX27 does not affect OTULIN catalytic activity, OTULIN-LUBAC binding or Met1-linked ubiquitin chain homeostasis. However, via association, OTULIN antagonizes SNX27-dependent cargo loading, binding of SNX27 to the VPS26A-retromer subunit and endosome-to-plasma membrane trafficking. Thus, we define an additional, non-catalytic function of OTULIN in the regulation of SNX27-retromer assembly and recycling to the cell surface.

PubMed: 31541095
DOI: 10.1038/s41467-019-12309-z

実験手法

X-RAY DIFFRACTION (2 Å)